亲爱的研友该休息了!由于当前在线用户较少,发布求助请尽量完整地填写文献信息,科研通机器人24小时在线,伴您度过漫漫科研夜!身体可是革命的本钱,早点休息,好梦!

Circulating Tumor DNA (ctDNA) for Plasma Genotyping and Disease Monitoring in ALK-Positive Anaplastic Lymphoma (ALK+ALCL): A Proof of Concept Study

间变性淋巴瘤激酶 微小残留病 克里唑蒂尼 碱性抑制剂 间变性大细胞淋巴瘤 数字聚合酶链反应 医学 淋巴瘤 内科学 ROS1型 肿瘤科 癌症研究 生物 聚合酶链反应 癌症 基因 白血病 肺癌 遗传学 腺癌 恶性胸腔积液
作者
Damien Vasseur,Samuel Abbou,Ludovic Lacroix,Laurence Lamant,Pata-Merci Noémie,David Sibon,Francesco Facchinetti,Marc Deloger,Floriane Brayé,Véronique Minard‐Colin,Laurence Brugières,Étienne Rouleau,Luc Friboulet,Charlotte Rigaud
出处
期刊:Blood [Elsevier BV]
卷期号:142 (Supplement 1): 4375-4375
标识
DOI:10.1182/blood-2023-185808
摘要

Introduction Circulating tumor DNA (ctDNA) detection has not been reported yet in ALK-positive anaplastic large cell lymphoma (ALK+ALCL), a rare aggressive non-Hodgkin lymphoma with a peak incidence in children, adolescents and young adults. In this study, we aimed to evaluate whether ctDNA can be detected, characterized and used to monitor minimal residual disease (MRD) in ALK+ALCL. Patients and Methods Plasma samples were collected from 23 French patients diagnosed with ALK+ALCL between November 2020 and March 2023. Based on cell-free DNA (cfDNA) extracted from plasma, we performed shallow whole genome sequencing (shWGS) and a comprehensive genomic profiling (CGP) of more than 500 genes covered at a median depth of over 3000 unique reads to assess ctDNA content. In this study, we defined samples as positive if they had a tumor fraction over 3%, evaluated by shWGS analysis, or if ALK rearrangements were identified using CGP. Additionally, ALK rearrangement genomic breakpoint were defined by CGP analysis. For each patient, specific digital droplet PCR (ddPCR) assays were designed based on the identified breakpoints to monitor ctDNA content during the ALK+ALCL disease follow-up. Results The median age of patients at the time of diagnosis was 13 years (range: 4-54). Sixteen patients, (69.6%) received at least one ALK tyrosine kinase inhibitor (TKI). A total of 80 plasma samples were collected at various time points from the 23 patients, with a median of 3 samples per patient (range: 1 - 20). Four samples failed for DNA extraction, resulting in 76 samples available for molecular analysis Of the 76 samples, 43 (56.6%) were analyzed using shWGS, 19 (25%) using CGP among which, 14 were analyzed using both techniques. CGP was found to be a more sensitive method for detecting ctDNA in ALK+ALCL compared to shWGS, with 12 out of 14 samples (85.7%) tested positive with CGP, compared to 5 out of 14 samples (35.7%) with shWGS (p<0.01). Of the 19 samples tested with CGP, ALK rearrangement was identified in 14 samples (73.7%), with NPM1:: ALK fusion detected in 11 samples, and ATIC:: ALK, TRAF1:: ALK and EEF1G:: ALK detected in one sample each. The average tumor mutational burden was low, with 5.3 mutations per megabase (mut/Mb) (range: 0-14.5 mut/Mb). No microsatellite instability was detected. Amplification of MDM4 and MYC genes was observed in three patients each. ANKRD26 was the most frequently mutated gene in the study, with four patients affected. LRP1B, epigenetic modifiers such as EP300 and KMT2A, and TP53 were mutated in three patients each. Interestingly, CGP allowed the identification of the ALK:c.3520T>C;p.(Phe1174Leu) mutation in a plasma sample collected during disease progression while the patient was on long lasting crizotinib therapy. Finally, we monitored MRD, based on ctDNA detection in 49 samples from 12 patients using ddPCR assays. Our results were compared with the established gold standard for MRD monitoring in ALK+ALCL, i.e. RT-PCR on circulating cells performed on the same samples. The ddPCR assay showed a 87% sensitivity, 100% specificity, 100% positive predictive value, and 83% negative predictive value. However, four samples had false-negative results due to pre-analytical sampling issues. These samples had been stored at room temperature without undergoing centrifugation for more than 24 hours. Conclusion To date, this study is the first to report on the feasibility and clinical value of ctDNA for the management of ALK+ALCL patients. CGP demonstrated high sensitivity in detecting ctDNA, identifying the genomic breakpoint within the ALK gene and, for the first time in ALK+ALCL, detecting resistance mutations to ALK TKI. Additionally, our unique patient-specific ddPCR approach was proven to be a cost-effective method for MRD monitoring. Altogether, these findings serve as a proof-of-concept for the development of ctDNA techniques in the clinical management of ALK+ALCL.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
摆渡人完成签到,获得积分10
5秒前
提桶跑路完成签到 ,获得积分10
7秒前
温柔的天奇完成签到 ,获得积分10
11秒前
实验耗材完成签到 ,获得积分10
18秒前
19秒前
lhlhl完成签到,获得积分10
23秒前
25秒前
27秒前
小小林发布了新的文献求助10
32秒前
zl13332完成签到 ,获得积分10
32秒前
33秒前
通通完成签到 ,获得积分10
35秒前
hhh完成签到 ,获得积分10
40秒前
48秒前
51秒前
51秒前
SUT文献战神完成签到,获得积分10
53秒前
董可以发布了新的文献求助10
54秒前
小二郎应助董可以采纳,获得10
1分钟前
花陵完成签到 ,获得积分10
1分钟前
含糊的无声完成签到 ,获得积分10
1分钟前
hxn完成签到,获得积分20
1分钟前
1分钟前
小张完成签到 ,获得积分10
1分钟前
jiafang完成签到,获得积分10
1分钟前
scholar丨崔发布了新的文献求助10
1分钟前
want_top_journal完成签到,获得积分10
1分钟前
1分钟前
scholar丨崔完成签到,获得积分10
1分钟前
1分钟前
2分钟前
简单的沛蓝完成签到 ,获得积分10
2分钟前
JIAN完成签到 ,获得积分10
2分钟前
Jasper应助hxn采纳,获得30
2分钟前
xxx完成签到,获得积分10
2分钟前
2分钟前
Green完成签到,获得积分10
2分钟前
斐嘿嘿发布了新的文献求助10
2分钟前
谢丹完成签到 ,获得积分10
2分钟前
寒冷的完成签到,获得积分10
2分钟前
高分求助中
The Mother of All Tableaux: Order, Equivalence, and Geometry in the Large-scale Structure of Optimality Theory 3000
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3990020
求助须知:如何正确求助?哪些是违规求助? 3532077
关于积分的说明 11256276
捐赠科研通 3270943
什么是DOI,文献DOI怎么找? 1805139
邀请新用户注册赠送积分活动 882270
科研通“疑难数据库(出版商)”最低求助积分说明 809228